CENTRAL MONOAMINES IN ACUTE-PHASE REACTION

最近，我们发现去甲肾上腺素（NE）的热反应， 当它被微透析，而不是微注射到 清醒豚鼠的视前区（PO）;即，NE产生了下降 而不是核心温度（Tco）的上升。 我们的研究表明， 微量注射NE后Tco升高主要是由于前列腺素E2 由于显微注射引起的组织损伤而释放的前列腺素E2（PGE 2） 手术本身，而不是由于药物，即，是人工制品 我们的微透析数据进一步表明， 内源性NE和PGE 2之间的拮抗作用;似乎它们的相对 PO中的浓度可能相互影响Tco。 的首要目标 因此，这项拟议的研究是评估这种明显的功能性NE- PGE 2拮抗作用。 最近的各种其他研究表明， 对体内或体外给予NE的不同反应 取决于NE的剂量，这些不同的作用 由不同的去甲肾上腺素能受体亚型介导。 亚型 人口和密度也被证明是不恒定的，受 在一定条件下改变。 由于不同的体温调节 据报道，中枢给予NE的效果取决于 剂量和各种其他条件，本研究的第二个目的 是确定对NE的热响应的方向是否 肾上腺素能受体亚型依赖性，并探讨对 选定实验条件下的热响应。 第三个目标 本研究旨在阐明NE在发热过程中的作用， 在上述假设的背景下，由于文献的作用， 发热反应中的中枢NE虽然广泛，但尚无定论， 可能是因为所有实验中使用的实验条件的可变性， 研究。 评估这种药物的内在体温调节作用 发射机将变得更容易，现在更具体的可用性 受体激动剂和拮抗剂，并通过使用微透析， 最大限度地减少创伤反应的混淆效应， 给药方式。 这项研究的结果应该有助于 解决早期研究结果之间的差异，并澄清NE的作用 体温的中央控制。 它们也可能与 涉及下丘脑NE的其他功能，例如，在 神经内分泌和免疫系统之间的相互作用。

Recently, we found that the thermal response to norepinephrine (NE) differed unexpectedly when it was microdialyzed, rather microinjected, into the preoptic area (PO) of conscious guinea pigs; i.e., NE produced a fall rather than a rise in core temperature (Tco). Our studies showed that the Tco rise following microinjected NE was due largely to prostaglandin E2 (PGE2) released as a result of tissue injury caused by the microinjection procedure itself, and was not due to the drug, i.e., it was artefactual. Our microdialysis data further suggested that there exists a functional antagonism between endogenous NE and PGE2; it appeared that their relative concentrations in the PO might mutually influence Tco. The first aim of this proposed study, therefore, is to evaluate this apparent functional NE- PGE2 antagonism. Various other studies have lately indicated that different responses to NE administration in vivo or application in vitro are activated depending on the NE dose, and that these different effects are mediated by different noradrenergic receptor subtypes. Subtype populations and densities have also been shown to be inconstant, subject to change under certain conditions. Since the different thermoreregulatory effects of centrally administrated NE have also been reported to depend on dosage and various other conditions, the second aim of this proposed study is to determine whether the direction of thermal responses to NE is adrenoceptor subtype-dependent, and to investigate the influence on the thermal response of selected experimental conditions. The third aim of the present study is to delineate the function(s) of NE during fever in the context of the above hypotheses, since the literature on the role of central NE in the febrile response, though extensive, is inconclusive, probably because of the variability of experimental conditions used in all the studies. Evaluation of the intrinsic thermoregulatory effects of this transmitter will be made easier by the availability now of more specific receptor agonists and antagonists and by the use of microdialysis, which minimizes the confounding effects of traumatic reactions that affect other modes of drug administration. The results of this study should help to resolve the discrepancies among earlier findings and clarify the role of NE in the central control of body temperature. They may also be pertinent to other functions in which hypothalamic NE has been implicated, e.g., in the interactions between the neuroendocrine and immune systems.